The PI3K/AKT/mTOR signaling pathway regulates various important cell functions such as cell proliferation, apoptosis resistance, and glycometabolism. The pathway is known to be hyperactive in a broad range of malignant tumors (Non-Patent Literature 1). Clinical trials have been conducted on many PI3K/AKT/mTOR inhibitors used as an antitumor agent (e.g., PI3K inhibitor, AKT inhibitor, mTOR inhibitor, or PI3K-mTOR dual inhibitor). However, particularly in clinical trials using a PI3K or AKT-targeting inhibitor as a single drug, none of these have yet to demonstrate satisfactory clinical benefits (Non-Patent Literature 2).
Molecularly targeted drugs, such as PI3K/AKT/mTOR inhibitors, may typically exhibit high potency on tumor cells in which the target molecules are highly expressed or hyperactive. It is thus important to stratify patients by using a therapeutic efficacy predictive marker to select a group of patients for whom beneficial effects are expected (Non-Patent Literature 3). As for PI3K/AKT/mTOR inhibitors, PIK3CA mutation, PTEN deletion, and the like have been examined as a therapeutic efficacy predictive marker in clinical practice (Non-Patent Literature 4).
As noted above, a variety of PI3K/AKT/mTOR inhibitors have been intensively developed. Nonetheless, their therapeutic efficacy on all cancer patients has remained unsatisfactory, and there has been found no therapeutic efficacy predictive markers capable of stratifying patients to select a group of patients that are likely to sufficiently respond to the PI3K/AKT/mTOR inhibitors.